Our major objective is to gain a better understanding of the relationship between molecular structure, biologic function and expression of antigens on the surface of human lymphocytes. To this end we have developed isolation procedures for HL-A antigens from cultured cells and from serum involving fractional salting out, gel filtration, ion exchange chromatography, anti beta 2 - microglobulin immunoadsorbents and preparative acrylamide gel electrophoresis. Chemical analyses indicate a molecular weight of 33,000 for HL-A antigens. Molecules with different HL-A specificities vary in charge and lack detectable amounts of carbohydrate. A highly specific anti-HL- A (W24) xenantibody was produced in rabbits from purified serum derived HL-A antigens. This antiserum is now being utilized in NIH typing trays. Isolation and partial characterization of other cell surface markers such as complement (C3b and C3d) receptors was also accomplished. Disulfide bridges but not free SH-groups appear to be crucial for the functionality of C3b receptors.